Gut microbiota dysbiosis is associated with inflammation and bacterial translocation in mice with CCl4-induced fibrosis

• Published in: PloS one Vol. 6; no. 7; p. e23037
• Main Authors: Gómez-Hurtado, Isabel, Santacruz, Arlette, Peiró, Gloria, Zapater, Pedro, Gutiérrez, Ana, Pérez-Mateo, Miguel, Sanz, Yolanda, Francés, Rubén
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.07.2011; Public Library of Science (PLoS)
• Subjects: Anaerobic treatment; Animals; Bacteria; Bacteria - classification; Bacteria - genetics; Bacteria - metabolism; Bacterial infections; Bacterial Translocation; Biodiversity; Biology; Biomarkers - metabolism; Blood; Campylobacter coli; Campylobacter jejuni; Carbon; Carbon tetrachloride; Carbon Tetrachloride Poisoning; CCL4 protein; Cirrhosis; Clostridium; Deoxyribonucleic acid; Digestive system; Digestive tract; DNA; DNA, Bacterial - genetics; Dysbacteriosis; Enterobacteriaceae; Feces; Feces - microbiology; Female; Fibrosis; Gastrointestinal Tract - microbiology; Gastrointestinal Tract - pathology; Gene expression; Gene Expression Profiling; Identification; Inflammation; Inflammation - complications; Inflammation - pathology; Inflammatory response; Interleukin 6; Intestinal microflora; Intestine; Irritable bowel syndrome; Lactobacillus; Laparotomy; Leukocytes (neutrophilic); Liver; Liver cirrhosis; Liver Cirrhosis - chemically induced; Liver Cirrhosis - complications; Liver Cirrhosis - pathology; Liver Cirrhosis - surgery; Lymph nodes; Medicine; Meningitis; Metagenome - genetics; Mice; Mice, Inbred BALB C; Oral administration; Pediococcus; Permeability; Quality; Real-Time Polymerase Chain Reaction; Ribosomal DNA; Shigella; Translocation; Tumor necrosis factor-α; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0023037

Gut is the major source of endogenous bacteria causing infections in advanced cirrhosis. Intestinal barrier dysfunction has been described in cirrhosis and account for an increased bacterial translocation rate. We hypothesize that microbiota composition may be affected and change along with the induction of experimental cirrhosis, affecting the inflammatory response. Progressive liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at weeks 6, 10, 13 and 16 in a subgroup of treated mice (n = 6/week) and control animals (n = 4/week). Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected at laparotomies. Fibrosis grade, pro-fibrogenic genes expression, gut bacterial composition, bacterial translocation, host's specific butyrate-receptor GPR-43 and serum cytokine levels were measured. Expression of pro-fibrogenic markers was significantly increased compared with control animals and correlated with the accumulated dose of carbon tetrachloride. Bacterial translocation episodes were less frequent in control mice than in treated animals. Gram-positive anaerobic Clostridia spp count was decreased in treated mice compared with control animals and with other gut common bacterial species, altering the aerobic/anaerobic ratio. This fact was associated with a decreased gene expression of GPR43 in neutrophils of treated mice and inversely correlated with TNF-alpha and IL-6 up-regulation in serum of treated mice along the study protocol. This pro-inflammatory scenario favoured blood bacterial translocation in treated animals, showing the highest bacterial translocation rate and aerobic/anaerobic ratio at the same weeks. Gut microbiota alterations are associated with the development of an inflammatory environment, fibrosis progression and bacterial translocation in carbon tetrachloride-treated mice.